The proposed research has as its long term a detailed elucidation of the interaction of amino acids and hormones, specifically glucagon and insulin in the regulation of gluconeogenesis in physiologic and pathologic circumstances such as diabetes, obesity, exercise, pregnancy, starvation and trauma. Specifically the relative importance of the liver and peripheral tissues in glucose and protein assimilation will be examined in normal and diabetic subjects. The effects of physiologic increments in glucagon on glucose, amino acid, and fatty acid metabolism will be investigated in normal and diabetic subjects. The role of glucagon in diabetes will be further examined by comparing the endogenous secretory rate and metabolic clearance rate of glucagon in normal and diabetic subjects. The effects of hyperketonemia on muscle amino acid output will be evaluated using the isolated rat diaphragm. Glucoregulatory mechanisms in exercise will be examined by observing the splanchnic glucose response to infusion of glucose and/or insulin during exercise.